U.S. Pat. No. 5,654,307 which is herein incorporated by reference discloses bicyclic compounds which includes a series of 4,6-disubstituted pyrido[3,4-d]pyrimidines.
The compounds disclosed in the above United States Patent are useful in inhibiting the epidermal growth factor receptor and related receptors and, in particular, their tyrosine kinase activity, and thus are useful in the treatment of proliferative diseases including cancer, psoriasis, proliferative glomerulonephritis and diabetes-induced renal disease, pancreatitis, and as contraceptives. The aforementioned compounds have been prepared by a synthetic route which affords the target compounds in extremely low yields, i.e., in less than 0.34% overall yield from the starting material, 2-chloro-5-nitropyridine, requires chromatographic purification at several stages and furthermore, is difficult to conduct on a large scale.
The object of the present invention is an improved process for preparing the compounds described above on a large scale using inexpensive starting materials.